Maintaining the male germline: regulation of spermatogonial stem cells

Caires, Kyle C.; Broady, Johnathan; McLean, Daniel G.

doi:10.1677/joe-09-0275

Cited by 85 publications

(63 citation statements)

References 95 publications

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“…In addition, 30-35% of Gdnf global Het mice had renal defects (49,53). In vitro studies since have demonstrated that GDNF regulates expression of genes in SSCs that influence their self-renewal and differentiation (1,3,54). Because GDNF has a critical role in multiple developmental processes in addition to spermatogenesis, it remained uncertain whether the perturbations of SSC development in vivo were due to direct effects on SSCs or indirect effects of total GDNF levels.…”

Section: Discussionmentioning

confidence: 99%

“…They are a minor fraction of the undifferentiated spermatogonia in the basal compartment. The other undifferentiated spermatogonia (progenitors) give rise to differentiating spermatogonia that proliferate mitotically to progress on a developmental pathway toward becoming spermatocytes (3,4). Our current understanding of the progression of SSCs to differentiating spermatogonia comes mainly from cell kinetic studies, germ cell transplantation assays, and the use of molecular markers that identify different populations of spermatogonia.…”

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confidence: 99%

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Targeting theGdnfGene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development

Chen

Willis

Eddy

2016

Proc. Natl. Acad. Sci. U.S.A.

157

128

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Spermatogonial stem cells (SSCs) are a subpopulation of undifferentiated spermatogonia located in a niche at the base of the seminiferous epithelium delimited by Sertoli cells and peritubular myoid (PM) cells. SSCs self-renew or differentiate into spermatogonia that proliferate to give rise to spermatocytes and maintain spermatogenesis. Glial cell line-derived neurotrophic factor (GDNF) is essential for this process. Sertoli cells produce GDNF and other growth factors and are commonly thought to be responsible for regulating SSC development, but limited attention has been paid to the role of PM cells in this process. A conditional knockout (cKO) of the androgen receptor gene in PM cells resulted in male infertility. We found that testosterone (T) induces GDNF expression in mouse PM cells in vitro and neonatal spermatogonia (including SSCs) co-cultured with T-treated PM cells were able to colonize testes of germ cell-depleted mice after transplantation. This strongly suggested that T-regulated production of GDNF by PM cells is required for spermatogonial development, but PM cells might produce other factors in vitro that are responsible. In this study, we tested the hypothesis that production of GDNF by PM cells is essential for spermatogonial development by generating mice with a cKO of the Gdnf gene in PM cells. The cKO males sired up to two litters but became infertile due to collapse of spermatogenesis and loss of undifferentiated spermatogonia. These studies show for the first time, to our knowledge, that the production of GDNF by PM cells is essential for undifferentiated spermatogonial cell development in vivo.spermatogonial stem cell | stem cell niche | male fertility | spermatogenesis | conditional gene targeting T he seminiferous epithelium is separated by tight junctions between Sertoli cells into a luminal compartment containing spermatocytes and spermatids and a basal compartment containing spermatogonial stem cells (SSCs) and spermatogonia. The basal compartment is bounded above and on the sides by Sertoli cells and below by the basement membrane of the seminiferous tubule and a layer of peritubular myoid (PM) cells. SSCs are thought to reside in a microenvironmental niche in the basal compartment, where extrinsic cues influence their decision to either self-renew or enter the pathway of spermatogonial development (1, 2). They are a minor fraction of the undifferentiated spermatogonia in the basal compartment. The other undifferentiated spermatogonia (progenitors) give rise to differentiating spermatogonia that proliferate mitotically to progress on a developmental pathway toward becoming spermatocytes (3, 4). Our current understanding of the progression of SSCs to differentiating spermatogonia comes mainly from cell kinetic studies, germ cell transplantation assays, and the use of molecular markers that identify different populations of spermatogonia.The leading model for spermatogonial development specifies that when SSCs divide, they either self-renew by becoming two type A-single (A s ) spermato...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Targeting theGdnfGene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development

Chen

Willis

Eddy

2016

Proc. Natl. Acad. Sci. U.S.A.

157

128

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“…The numbers of these stem cells in testes is approximately 0.03 % of the total testicular cell population in the adult mouse [28,36]. Additionally, the establishment and maintenance of a niche's microenvironment in the seminiferous tubules of the testis is important to regulate the SSC population and its function [4]. These cells are located close to several supporting somatic cells and the basement membrane or extracellular matrix (ECM) of seminiferous tubules, which may contribute to the formation of the SSC niche.…”

Section: Introductionmentioning

confidence: 99%

Behavior of mouse spermatogonial stem-like cells on an electrospun nanofibrillar matrix

Malek

Kohram

Shahverdi

et al. 2012

J Assist Reprod Genet

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Purpose Spermatogonial stem cells are affected by the interactions of extrinsic signals produced by components of the microenvironment niche, in addition to the chemical and physical properties of the extracellular matrix. Therefore, this study was initiated to assess the interaction of these cells on a synthetic nanofibrillar extracellular matrix that mimicked the geometry and nanotopography of the basement membrane for cellular growth. Methods This study has used a variety of experimental approaches to investigate the interaction of mouse neonatalderived spermatogonial stem-like cells on a synthetic random oriented three-dimensional nanofibrillar matrix composed of electrospun polyamide nanofibers (Ultra-Web™).Results Spermatogonial stem-like cell colonies were characterized by their ability to express α6-integrin, Thy-1, PLZF, and β1-integrin. After culture of cells on the nanofibrillar surfaces for 7 days, the number of colonies, the number of cells in each colony, and the average area of colonies were increased (P<0.05). However, the expression difference of related markers in both groups was not significant. A significantly higher proliferation and survival was observed in the nanofibrillar group (P<0.05). After transplantation into the testes of busulfan-treated adult mice, spermatogonial stem-like cell colonies that were cultured on the nanofibrillar surface demonstrated functionality, as verified by their ability to migrate to the seminiferous basal membrane, where they produced additional colonies. Conclusions These results have suggested that electrospun nanofibrillar surfaces could provide a more favorable microenvironment for in vitro short term culture of spermatogonial stem-like cell colonies.

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“…In both cases, they are not produced in greater differentiation (Type A 1 -A 4 , Intermediated, spermatocytes and spermatids; Caires et al, 2010). A key step in studying the biology of SSCs is to determine their gene expression profile.…”

Section: Characterization Of Spermatogonial Stem Cellsmentioning

confidence: 99%

“…However, a scarce knowledge of molecular markers has been accumulated in recent years (Kokkinaki et al, 2010). Some research groups have demonstrated that glial cell-.derived neurotrophic factor (GDNF) is the most essential factor for SSC self-renewal and in vitro maintenance in rodents (Caires et al, 2010;Ryu et al, 2005;Meng et al, 2000;Kubota et al, 2004a,b;Kanatsu-Shinohara et al, 2005;Kanatsu-Shinohara et al, 2008;and Braydish-Stalle et al, 2005) and that GDNF receptor (GFRA1) is expressed by SSC/progenitor cells (Naughton et al, 2006;Hofmann et al, 2005 andHe et al, 2007). The activation of GDNF pathway probably is related with other pathways that promote the proliferation and the self-renewal of SSCs (Caires et al, 2010;Jijiwa et al, 2004;Braydich-Stolle et al, 2007;Oatley et al, 2007 andLee et al, 2006).…”

Section: Characterization Of Spermatogonial Stem Cellsmentioning

confidence: 99%